D2 dopamine receptor regulation of learning, sleep and plasticity.

Dopamine and sleep have been independently linked with hippocampus-dependent learning. Since D2 dopaminergic transmission is required for the occurrence of rapid-eye-movement (REM) sleep, it is possible that dopamine affects learning by way of changes in post-acquisition REM sleep. To investigate this hypothesis, we first assessed whether D2 dopaminergic modulation in mice affects novel object preference, a hippocampus-dependent task. Animals trained in the dark period, when sleep is reduced, did not improve significantly in performance when tested 24h after training. In contrast, animals trained in the sleep-rich light period showed significant learning after 24h. When injected with the D2 inverse agonist haloperidol immediately after the exploration of novel objects, animals trained in the light period showed reduced novelty preference upon retesting 24h later. Next we investigated whether haloperidol affected the protein levels of plasticity factors shown to be up-regulated in an experience-dependent manner during REM sleep. Haloperidol decreased post-exploration hippocampal protein levels at 3h, 6h and 12h for phosphorylated Ca(2+)/calmodulin-dependent protein kinase II, at 6h for Zif-268; and at 12h for the brain-derived neurotrophic factor. Electrophysiological and kinematic recordings showed a significant decrease in the amount of REM sleep following haloperidol injection, while slow-wave sleep remained unaltered. Importantly, REM sleep decrease across animals was strongly correlated with deficits in novelty preference (Rho=0.56, p=0.012). Altogether, the results suggest that the dopaminergic regulation of REM sleep affects learning by modulating post-training levels of calcium-dependent plasticity factors.

Feasibility of ethanol production from coffee husks.

The objective of this work was to evaluate the feasibility of ethanol production by fermentation of coffee husks by Saccharomyces cerevisiae. Batch fermentation studies were performed employing whole and ground coffee husks, and aqueous extract from ground coffee husks. It was observed that fermentation yield decreased with an increase in yeast concentration. The best results were obtained for the following conditions: whole coffee husks, 3 g yeast/l substrate, temperature of 30 degrees C. Under these conditions ethanol production was 8.49 +/- 0.29 g/100 g dry basis (13.6 +/- 0.5 g ethanol/l), a satisfactory value in comparison to literature data for other residues such as corn stalks, barley straw and hydrolyzed wheat stillage (5-11 g ethanol/l). Such results indicate that coffee husks present excellent potential for residue-based ethanol production.

[Interferon beta 1-a in multiple sclerosis: 1-year experience in 62 patients]. / Interferon beta 1-a na esclerose múltipla: experiência de um ano em 62 pacientes.

We report the results of a trial of interferon beta 1-a in 62 ambulatory patients with relapsing-remitting multiple sclerosis. Entry criteria included EDSS of 0 to 5.5 and at least two exacerbations in the previous 2 years. The patients received 3 million international units by subcutaneous injections three times a week. The end points were differences in exacerbation rate and treatment effect on disease progression. The annual exacerbation rate for patients that did not take the interferon beta 1-a was 1.32 and for the patients under medication 0.63. The EDSS score in patients that did not take the mediaction was 4.7 and 2.0 for the patients with interferon beta 1-a. Interferon beta 1-a was well tolerated and 85% of patients completed 1 year treatment.

Effects of mercury on the isolated perfused rat tail vascular bed are endothelium-dependent.

The effects of mercury on vascular smooth muscle results in vasoconstriction, but the mechanism of this action is not elucidated yet. To investigate this issue we examined the effects of HgCl(2) in the isolated rat tail vascular bed. The tail artery was dissected, cannulated, and perfused at a constant flow (2.5 ml/min) with Krebs solution plus EDTA 0.03 mM at 36 degrees C. After equilibration for 30 min the effects of increasing concentrations of HgCl(2) (0.5, 1, 2, 5, and 10 microM) on the perfusion pressure were investigated. Concentrations of HgCl(2), 2 microM and above, significantly increased perfusion pressure. Blockade of alpha receptors (prazosin 84 ng/ml) did not alter the responses to HgCl(2), suggesting that the metal does not induce the release of neurotransmitters from sympathetic nerve terminals. To investigate the possible role of endothelium on the vasoconstriction produced by HgCl(2), preparations were precontracted with 10(-7) M phenylepherine or perfused with 5 microM HgCl(2) for 20 min. Acetylcholine-vasodilated preparations precontracted with phenylepherine demonstrating the integrity of the endothelial nitric oxide-releasing mechanism. In contrast, after perfusion with 5 microM HgCl(2), the vasodilation produced by acetylcholine was abolished. In the presence of either phenylephrine or HgCl(2) the effects of sodium nitroprusside remained unchanged. Pretreatment with 30 microM indomethacin fully prevented the HgCl(2)-induced vasoconstriction. However, the endothelium-dependent vasodilation in response to acetylcholine was significantly reduced after indomethacin plus HgCl(2) treatment, meanwhile the vasodilation produced by nitroprusside remained unchanged. Pretreatment with L-arginine (1 mM) did not prevent the vasoconstriction induced by HgCl(2), nor did it restore the ability of acetylcholine to produce vasodilation, and it did not alter the response to sodium nitroprusside. The possibility of HgCl(2)'s actions mediated by the formation of free radicals was also investigated. The administration of 10 mM histidine significantly reduced the vasoconstrictor response if used before HgCl(2) treatment without improving the reduced vasodilation produced by acetylcholine. These results are consistent with the hypothesis that the vasoconstriction produced by HgCl(2) may be mediated by the formation of superoxide anions, stimulating the production of a COX-derived vasoconstrictor agent and by reducing the endothelial vasodilator activity.

Reactivity of the isolated perfused rat tail vascular bed.

Isolated segments of the perfused rat tail artery display a high basal tone when compared to other isolated arteries such as the mesenteric and are suitable for the assay of vasopressor agents. However, the perfusion of this artery in the entire tail has not yet been used for functional studies. The main purpose of the present study was to identify some aspects of the vascular reactivity of the rat tail vascular bed and validate this method to measure vascular reactivity. The tail severed from the body was perfused with Krebs solution containing different Ca2+ concentrations at different flow rates. Rats were anesthetized with sodium pentobarbital (65 mg/kg) and heparinized (500 U). The tail artery was dissected near the tail insertion, cannulated and perfused with Krebs solution plus 30 microM EDTA at 36 degrees C and 2.5 ml/min and the procedures were started after equilibration of the perfusion pressure. In the first group a dose-response curve to phenylephrine (PE) (0.5, 1, 2 and 5 micrograms, bolus injection) was obtained at different flow rates (1.5, 2.5 and 3.5 ml/min). The mean perfusion pressure increased with flow as well as PE vasopressor responses. In a second group the flow was changed (1.5, 2, 2.5, 3 and 3.5 ml/min) at different Ca2+ concentrations (0.62, 1.25, 2.5 and 3.75 mM) in the Krebs solution. Increasing Ca2+ concentrations did not alter the flow-pressure relationship. In the third group a similar protocol was performed but the rat tail vascular bed was perfused with Krebs solution containing PE (0.1 microgram/ml). There was an enhancement of the effect of PE with increasing external Ca2+ and flow. PE vasopressor responses increased after endothelial damage with air and CHAPS, suggesting an endothelial modulation of the tone of the rat tail vascular bed. These experiments validate the perfusion of the rat tail vascular bed as a method to investigate vascular reactivity.

Reactivity of the isolated perfused rat tail vascular bed

Isolated segments of the perfused rat tail artery display a high basal tone when compared to other isolated arteries such as the mesenteric and are suitable for the assay of vasopressor agents. However, the perfusion of this artery in the entire tail has not yet been used for functional studies. The main purpose of the present study was to identify some aspects of the vascular reactivity of the rat tail vascular bed and validate this method to measure vascular reactivity. The tail severed from the body was perfused with Krebs solution containing different Ca2+ concentrations at different flow rates. Rats were anesthetized with sodium pentobarbital (65 mg/kg) and heparinized (500 U). The tail artery was dissected near the tail insertion, cannulated and perfused with Krebs solution plus 30 muM EDTA at 36 degrees Celsius and 2.5 ml/min and the procedures were started after equilibration of the perfusion pressure. In the first group a dose-response curve to phenylephrine (PE) (0.5, 1,2 and 5 mug, bolus injection) was obtained at different flow rates (1.5, 2.5 and 3.5 ml/min). The mean perfusion pressure increased with flow as well as PE vasopressor responses. In a second group the flow was changed (1.5,2,2.5,3 and 3.5 ml/min) at different Ca2+ concentrations (0.62, 1.25, 2.5 and 3.75 mM) in the Krebs solution. Increasing Ca2+ concentrations did not alter the flow-pressure relationship. In the third group a similar protocol was performed but the rat tail vascular bed was perfused with Krebs solution containing PE (0.1 mug/ml). There was an enhancement of the effects of PE with increasing external Ca2+ and flow. PE vasopressor responses increased after endothelial damage with air and CHAPS, suggesting an endothelial modulation of the tone of the rat tail vascular bed. These experiments validate the perfusion of the rat tail vascular bed as a method to investigate vascular reactivity.